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Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury.
Exp Neurol 2004; 190(1):192-203EN

Abstract

Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). This immunohistochemical study determined the extent of AD-related changes in temporal cortex resected from individuals treated surgically for severe TBI. Antisera generated against Abeta species (total Abeta, Abeta(1-42), and Abeta(1-40)), the C-terminal of the Abeta precursor protein (APP), apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau, ubiquitin, alpha-, beta-, and gamma-synuclein) were used to examine the extent of Abeta plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18-64 years). Diffuse cortical Abeta deposits were observed in one third of subjects (aged 35-62 years) as early as 2 h after injury, with only one (35-year old) individual exhibiting "mature", dense-cored plaques. Plaque-like deposits, neurons, glia, and axonal changes were also immunostained with APP and apoE antibodies. In plaque-positive cases, the only statistically significant change in cellular immunostaining was increased neuronal APP (P = 0.013). There was no significant correlation between the distribution of Abeta plaques and markers of neuronal degeneration. Diffuse tau immunostaining was localized to neuronal cell soma, axons or glial cells in a larger subset of individuals. Tau-positive, neurofibrillary tangle (NFT)-like changes were detected in only two subjects, both of more advanced age and who were without Abeta deposits. Other neurodegenerative changes, evidenced by ubiquitin- and synuclein-immunoreactive neurons, were abundant in the majority of cases. Our results demonstrate a differential distribution and course of intra- and extra-cellular AD-like changes during the acute phase following severe TBI in humans. Abeta plaques and early evidence of neuronal degenerative changes can develop rapidly after TBI, while fully developed NFTs most likely result from more chronic disease- or injury-related processes. These observations lend further support to the hypothesis that head trauma significantly increases the risk of developing pathological and clinical symptoms of AD, and provide insight into the molecular mechanisms that initiate these pathological cascades very early during severe brain injury.

Authors+Show Affiliations

Department of Neurology, University of Pittsburgh School of Medicine, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15473992

Citation

Ikonomovic, Milos D., et al. "Alzheimer's Pathology in Human Temporal Cortex Surgically Excised After Severe Brain Injury." Experimental Neurology, vol. 190, no. 1, 2004, pp. 192-203.
Ikonomovic MD, Uryu K, Abrahamson EE, et al. Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Exp Neurol. 2004;190(1):192-203.
Ikonomovic, M. D., Uryu, K., Abrahamson, E. E., Ciallella, J. R., Trojanowski, J. Q., Lee, V. M., ... DeKosky, S. T. (2004). Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Experimental Neurology, 190(1), pp. 192-203.
Ikonomovic MD, et al. Alzheimer's Pathology in Human Temporal Cortex Surgically Excised After Severe Brain Injury. Exp Neurol. 2004;190(1):192-203. PubMed PMID: 15473992.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. AU - Ikonomovic,Milos D, AU - Uryu,Kunihiro, AU - Abrahamson,Eric E, AU - Ciallella,John R, AU - Trojanowski,John Q, AU - Lee,Virginia M-Y, AU - Clark,Robert S, AU - Marion,Donald W, AU - Wisniewski,Stephen R, AU - DeKosky,Steven T, PY - 2004/01/22/received PY - 2004/05/20/revised PY - 2004/06/10/accepted PY - 2004/10/12/pubmed PY - 2005/1/14/medline PY - 2004/10/12/entrez SP - 192 EP - 203 JF - Experimental neurology JO - Exp. Neurol. VL - 190 IS - 1 N2 - Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). This immunohistochemical study determined the extent of AD-related changes in temporal cortex resected from individuals treated surgically for severe TBI. Antisera generated against Abeta species (total Abeta, Abeta(1-42), and Abeta(1-40)), the C-terminal of the Abeta precursor protein (APP), apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau, ubiquitin, alpha-, beta-, and gamma-synuclein) were used to examine the extent of Abeta plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18-64 years). Diffuse cortical Abeta deposits were observed in one third of subjects (aged 35-62 years) as early as 2 h after injury, with only one (35-year old) individual exhibiting "mature", dense-cored plaques. Plaque-like deposits, neurons, glia, and axonal changes were also immunostained with APP and apoE antibodies. In plaque-positive cases, the only statistically significant change in cellular immunostaining was increased neuronal APP (P = 0.013). There was no significant correlation between the distribution of Abeta plaques and markers of neuronal degeneration. Diffuse tau immunostaining was localized to neuronal cell soma, axons or glial cells in a larger subset of individuals. Tau-positive, neurofibrillary tangle (NFT)-like changes were detected in only two subjects, both of more advanced age and who were without Abeta deposits. Other neurodegenerative changes, evidenced by ubiquitin- and synuclein-immunoreactive neurons, were abundant in the majority of cases. Our results demonstrate a differential distribution and course of intra- and extra-cellular AD-like changes during the acute phase following severe TBI in humans. Abeta plaques and early evidence of neuronal degenerative changes can develop rapidly after TBI, while fully developed NFTs most likely result from more chronic disease- or injury-related processes. These observations lend further support to the hypothesis that head trauma significantly increases the risk of developing pathological and clinical symptoms of AD, and provide insight into the molecular mechanisms that initiate these pathological cascades very early during severe brain injury. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15473992/Alzheimer's_pathology_in_human_temporal_cortex_surgically_excised_after_severe_brain_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014488604002420 DB - PRIME DP - Unbound Medicine ER -